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Nucleophilic Aromatic Substitution Reactions of Novel 5-(2-Methoxyphenyl)tetrazole Derivatives with Organolithium Reagents

“…The tetrazole ring system has attracted considerable attention in recent years, especially among medicinal chemists, as a potential surrogate for cis -peptide linkage, carboxylic acids, and others . Driven in particular by the widespread incorporation of tetrazole functionality into angiotensin II antagonist structures, several excellent new synthetic methods have recently been described for the construction, protection, and transformation of this heterocycle …”

“…Ortho-directed lithiation of a suitably N -protected 5-(aryl)tetrazole, followed by transmetalation and Pd 0 -catalyzed coupling with an aryl halide, is a particularly useful sequence for the preparation of highly functionalized 5-(2-biaryl)tetrazoles; 2g,3m however, during the course of a research program toward angiotensin II antagonists we required a synthetic route to 5-(2-biaryl)tetrazoles that would obviate the need for transmetalation and heavy-metal catalysis in the coupling reaction. Aside from the expense and potential concerns associated with the recovery of Pd 0 L 4 catalysts from pilot-scale procedures, we observed that it was sometimes difficult to satisfactorily remove trace levels of palladium contamination from the final 5-(2-biaryl)tetrazole products except by inconvenient large-scale chromatographic purification.…”

Synthesis and Tuberculostatic Activity of Some Substituted Amino Acid Methyl Esters with Sym-Tetrazine Moieties

“…This class contains inhibitors of some vital MBT enzymes, in particular, dihydrofolate reductase [3]. Recently, we discovered the antituberculous activity of 2,5-disubstituted tetrazoles [4].…”